Over the past few decades, steadily increasing drug resistance in the treatment of infectious disease pose a serious problem in antimicrobial therapy and necessitates continuing research into novel classes of antimicrobials. Schiff bases are associated with diverse biocidal activities probably by virtue of a toxophoric C = N linkage and the importance of 1, 3, 4–oxadiazole as antimicrobial agent revealed from literature prompted us to undertake the synthesis of few novel 1, 3, 4–oxadiazole for evaluation as antimicrobial agents. A novel series of Schiff bases containing imidazo[2,1-b]-1,3,4-oxadiazole ring were synthesized and their antimicrobial activity was evaluated using disc diffusion method. Antimicrobial potential of synthesized compounds were evaluated against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Staphylococcus epidermidis, Pseudomonas fluorescens, Aspergillus niger and Candida albicans. Majority of the compounds were found to possess a broad spectrum of antimicrobial activities against all the pathogenic microorganisms tested including Pseudomonas fluorescens and Candida albicans responsible for nosocomial infection.